Brinda K. Rana, PhD, an Assistant Professor in the Department of Psychiatry at the University of California, San Diego (UCSD) School of Medicine, is applying for the K01 Mentored Research Scientist Development Award with primary mentor Dr. William Kremen and co-mentor Dr. Nicholas Schork. The goals of the proposed K01 training are to obtain training in (1) cognitive aging research;(2) research design;and (3) epigenetics. This training will enable Dr. Rana to reach her career goal of an independent researcher in the field of genomics of cognitive aging. The training objectives will be met through a combination of conducting the proposed research, participating in on-going cognitive assessments in Dr. Kremen's laboratory, visits with collaborators Michael Lyons and Lindon Eaves for training in twin methodology, and participation in workshops, courses, and seminars at the Stein Institute for Research in Aging. Dr. Rana's primary mentor is Dr. Kremen, an expert in neuropsychiatric assessments and aging research at UCSD and Principle Investigator on the Vietnam Era Twin Study of Aging (VETSA). Dr. Rana's co-mentor, Dr. Schork, a statistical geneticist at The Scripps Research Institute in La Jolla, CA who is developing DNA methylation methodologies. Drs. Lindon Eaves, Michael Lyons, and Michael Neale are collaborators on this project and will mentor Dr. Rana in twin methodology. Dr. Kun Zhang in the UCSD Department of Bioengineering is an expert in whole genome DNA methylation technologies, and will serve as an on-site consultant for DNA methylation studies. Dr. Shah Golshan will serve as a consultant for databasing large amounts of genomic data. The overall goal of the proposed research, "Genetic and Epigenetic Factors of Age-Related Cognitive Decline-A Twin Study," is to better understand genomic and environmental predictors of age-related neurocognitive changes through epigenetic studies. Specifically, the DNA samples and longitudinal phenotype data from the VETSA cohort will be used to address this goal. VETSA is an ongoing longitudinal study specifically designed to investigate the genetic and environmental contributors to cognitive processes over time with special features that include twin sampling of over 1200 twins that enables the estimation of heritability of phenotypes, detailed cognitive and related phenotype data on each individual, biochemical phenotypes such as cortisol levels, and longitudinal data on some cognitive and biochemical phenotypes. In addition, the phenotype data starts at midlife which allows for the identification of predictors of healthy cognitive aging. A combination of classical twin design, co-twin control design, and non-twin design will be used to determine the role of DNA methylation in cognitive and brain aging. PUBLIC HEALTH RELEVANCE: With the increasing population of aged individuals in the United States and outside, identifying inherited and acquired factors contributing to age-related neurocognitive decline and resilience from decline is becoming a priority. I propose to apply twin methodology on a unique cohort of subjects collected through the Vietnam Era Twin Study of Aging to identify epigenetic factors. The overall goal of this study is to better understand genomic and environmental predictors of age-related neurocognitive changes through DNA methylation studies.